The description relates to the production of ammonium gluconate in a process that involves ultrafiltration. The process utilizes relatively small amounts of reactants that result in an overall reduction in cost that is significant for large scale manufacture of gluconate.
The demand for metal gluconates is increasing due to their multiple applications in different industries. For example, sodium gluconate has utility as an environmentally friendly industrial detergent and calcium gluconate can be used for dietary calcium supplementation. Ferrous gluconate is used for iron supplementation of anemic patient while zinc gluconate is used as a zinc supplement in nutritional diets.
Current production techniques are directed to the manufacture of gluconic acid and sodium gluconate. The present production protocols tend to use relatively large amounts of costly starting materials. Inefficiencies in product purification result from relatively wasteful purification procedures that are required to remove residual reactants from the gluconic acid or sodium gluconate during manufacture. Moreover, present techniques are associated with inactivation of reagent enzymes when used.
Currently gluconic acid and its salts are produced by batch fermentation or using enzymes (U.S. Pat. No. 5,897,995). Batch fermentation utilizes Aspergillus niger that converts glucose to gluconic acid and its salts. (Greenfield, Paul F., Kittrell, James, R., Laurence, Robert L., (1975) xe2x80x9cInactivation of Immobilized Glucose Oxidase by Hydrogen Peroxidexe2x80x9d, Anal. Biochem., 65, PP 109-124. Weibel, Michael K., Bright, Harold J., (1971) xe2x80x9cThe Glucose Oxidase Mechanismxe2x80x9d, J. Biol. Chem., Vol. 246, May 10, pp 2734-2744. Gibson, Quesntin H., Swoboda, Bennett E. P., Massey, Vincent, (1964) xe2x80x9cKinetics and Mechanism of Action of Glucose Oxidasexe2x80x9d, J. Biol. Chem., Vol. 239, No. 11, pp 3927-3934. Nakamura, T., and Ogura, Y. L., (1963) J. Biolchem (Tokyo), 53, 2, pp 143. Nakamura, T., and Ogura, Y. L., (1962) J. Biotchem (Tokyo), 52, 3, pp 214. Bentley, R., and Neuberger, A., (1949) Biochem. J., 45, pp 584.) Some of the problems associated with fermentation production techniques include the use of complex media for growing microorganisms and associated increased complexity of purification Enzymatic production of gluconic acid or its salts tend to rely on relatively large amounts of reagents (U.S. Pat. No. 5,897,995 describes the use of glucose reagent at a concentration of at least 10% and preferably as high as 50%) U.S. Pat. No. 3,935,071 describes the conversion of glucose into gluconic acid using enzymes bound to a carrier (also FRA2 2029645, EP 017708) and separation of the gluconic acid by anion exchange chromatography.
In summary, the existing processes for the production of gluconates are cost inefficient for reasons that include: (a) use of excess costly starting materials and; (b) loss of product through purification procedures.
The inefficiencies and costs of current production techniques for gluconates are magnified during large scale production. Each reaction vessel or fermentor in the manufacture of gluconic acid may have a capacity of greater than 100,000 liters and multiple fermentors of this size are required to produce millions of pounds of gluconates. Any reduction in raw materials or handling would result in a significant cost reduction.
In addition to the cost of materials, existing production of gluconates generates substantial amounts of waste materials. Each production batch can generate millions of gallons of industrial as well as biological wastes. The large amount of industrial and biological wastes generated from conventional fermentation processes can pollute the city sewage system if the plant effluents are not treated extensively. Thus, the conventional fermentation process puts large burden to the city infrastructure of any community due to its large resource requirements and waste treatment facilities. Due to the increased demand of environmentally benign gluconates in industrial and pharmaceutical applications, any improvement in the cost and efficiency of production methods would be desirable.
In preferred embodiments of the invention, a method is provided for producing substantially pure ammonium gluconate, that includes the steps of (a) adding a first volume of a glucose solution in a glucose feed to a preparation of glucose oxidase in a reaction chamber and adding a second volume of ammonia in an ammonium feed to the reaction chamber for forming a reaction mixture containing ammonium gluconate; (b) removing a third volume of the reaction mixture; and (c) separating ammonium gluconate from the third volume by ultrafiltration to produce substantially pure ammonium gluconate. In a preferred embodiment of the invention, the preparation in the reaction chamber further includes catalase. The ammonia optionally is in liquid form or in gaseous form. The ammonium gluconate may be separated from the third volume removed from the reaction mixture through an ultrafiltration membrane to provide a retentate for returning to the reaction chamber and a permeate containing ammonium gluconate. The ammonium gluconate may be crystallized from the permeate. The glucose oxidase and/or catalase may be derived from a micro-organism, for example, Aspergillus niger.
Concerning amounts of reactant and catalyst, the glucose oxidase activity per unit weight of glucose may be maintained at less than 20 and optionally catalase activity per unit weight of glucose may be less than 800. A ratio of glucose oxidase to catalase activity may be less than 0.1. The reaction chamber may be maintained at a temperature of between 15xc2x0 C. and 40xc2x0 C. and the reaction occurs in the presence of oxygen of atmospheric air and optionally at a pH in the range of pH 4 to pH 8, for example pH 5 to pH 7. The concentration of glucose in the continuous feed may be maintained at less than 75% (w/v) in the reaction mixture and the concentration of glucose in the reaction chamber is maintained at less than about 10% (w/v) for example, less than 5% in the reaction mixture. The ammonia in the second volume has a concentration of 5%-30% (v/v). The ultrafiltration membrane may optionally have a pore size of molecular weight cut-off between 5,000 and 50,000.
In a preferred embodiment, glucose may have a conversion efficiency into ammonium gluconate of at least 90%.
In a preferred embodiment, a method for producing metal gluconates is provided that includes (a) adding a first volume of a glucose solution in a glucose feed to a preparation of glucose oxidase in a reaction chamber and adding a second volume of a metal base solution or suspension in a feed to the reaction chamber for forming a reaction mixture containing metal gluconate; (b) removing a third volume of the reaction mixture; and (c) separating metal gluconate from the third volume by ultrafiltration to produce substantially pure metal gluconate.
Accordingly, the metal gluconate may be crystallized from the permeate after ultrafiltration of the third volume. The metal base solution may be selected from the group consisting of sodium base, potassium base, calcium base, zinc base, ferrous base, magnesium base, manganese base and cuprous base solution and further may include a lithium base.